Glial cell line neurotrophic factor (GDNF) is a potent survival factor for several types of neurons. GDNF binds with high affinity to the GDNF-family receptor a-1 (GFRa-1) which is expressed in different brain areas. In the present study, by using anatomical techniques, we document the phenotypic diversity among GFRa-1 expressing neurons in the central nervous system (CNS). We found expression of GFRa-1 in GABA (g-aminobutyric acid) -containing neurons distributed in the cortex, reticular thalamic nucleus and septum. While high expression of GFRa-1 was often observed in cholinergic motoneurons in the spinal cord, very few septal cholinergic neurons were found to express GFRa-1. GFRa-1 transcripts were also detected in catecholaminergic neurons in the periventricular hypothalamic nucleus, dorsal raphe nucleus and locus ceruleus. Within the raphe nucleus, GFRa-1 expression was prominent in many serotonergic neurons and in few neurons containing the enzyme nitric oxide synthase (NOS). As GFRa-1 is activated by GDNF and GDNF-related neurotrophic factors, the widespread distribution of GFRa-1 in neurons with different phenotypes indicates that the neuronal activity of these neurons is likely to be affected by GDNF and GDNF-related neurotrophic factors. This would result in the regulation of diverse neuronal pathways in the adult brain.